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Biomedical subjects

Yuji Hiramatsu

Publications and source records attributed to Yuji Hiramatsu.

At least 19 recordsLinked to original sources
PubMed2006

In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope.

PURPOSE: NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells. EXPERIMENTAL DESIGN: In vitro stimulation of CD8 or CD4 T cells was determined by IFNgamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFNgamma. RESULTS: NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2-binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50). CONCLUSIONS: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.

Amino Acid Sequence↗
PubMed2006

Efficacy and prognostic implications of administering adjuvant chemotherapy to patients with endometrial cancer that is confined to the uterus.

OBJECTIVE: The purpose of this study was to determine the value of prognostic factors and to assess the efficacy of adjuvant chemotherapy in patients with endometrial cancer confined to the uterus. STUDY DESIGN: Patients surgically stage IB, IC and II endometrial cancer according to the International Federation of Gynecology and Obstetrics were enrolled in this study. Stage IIIA tumors with positive peritoneal cytology, in the absence of other evidence of extra uterine disease, were also included. RESULTS: One hundred and sixty-seven patients fulfilled the eligibility criteria and 58 patients (34.7%) underwent combination chemotherapy. Disease recurrence occurred in 10 patients within a median time of 17 months. Histologic grade 3 was an independent prognostic factor for both disease-free and overall survival rates. Fourteen of 23 patients with histologic grade 3 tumors received adjuvant chemotherapy consisting of cyclophosphamide (or etoposide), epirubicin and cisplatin (in 1989-1999) or paclitaxel, pirarubicin and carboplatin (in 2000-2002). The 5-year disease-free and overall survival rates for these individuals was 92.3%, a value significantly higher than those in patients who had not undergone chemotherapy (50.0%). CONCLUSIONS: Histologic grade of 3 is an independent prognostic marker in patients with endometrial cancer confined to the uterus and adjuvant chemotherapy might improve the survival rates in these patients.

Adult↗
PubMed2006

Replacement of the common atrioventricular valve with floating annuloplasty in a patient with univentricular physiology.

Significant common atrioventricular valve insufficiency is associated with increased mortality and morbidity in patients with univentricular physiology. Shortly after bidirectional cavopulmonary anastomosis and concomitant valvuloplasty, valve replacement was carried out using a floating annuloplasty technique reinforced by a Dacron strip in a patient with common atrioventricular valve insufficiency. The technique applied is described in detail.

Cardiac Surgical Procedures↗
PubMed2006

Parathyroid hormone-related protein as a potential tumor marker: a case report of ovarian clear cell carcinoma.

Hypercalcemia is one of the important paraneoplastic syndromes, mostly occurring in patients with advanced cancer. Clear cell carcinoma is known to be one of the most common histological subtypes of ovarian tumor associated with hypercalcemia. We present a case of ovarian clear cell carcinoma with hypercalcemia caused by elevated serum parathyroid hormone-related protein (PTHrP). PTHrP mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemical analysis in the primary and metastasis lesions. Serum calcium and PTHrP levels returned to normal after antihypercalcemic treatment and a radical operation, but they elevated along with the recurrence. Because tumor markers such as carcinoembryonic antigen, carbohydrate antigen (CA)125 and CA19-9 were unstable owing to the patient's liver cirrhosis and were not reliable data for management, serum calcium and PTHrP levels are shown to have been a potential indicator of the recurrence in this case.

Adenocarcinoma, Clear Cell↗
PubMed2006

A pitfall in ligation of intrahepatic shunting after Fontan type operation.

An 8-year-old boy experienced progressive cyanosis after a Fontan type operation. Under the guidance of intraoperative color Doppler we performed a transabdominal ligation of the accessory hepatic veins which drained into a common atrium. Reoperation was needed through a median sternotomy to eliminate residual shunting. Although intraoperative Doppler is useful to aid in the ligation of accessory veins while portal hypertension is monitored, intraoperative angiogram serves better to ensure the elimination of intrahepatic shunting in a transabdominal approach.

Angiography↗
PubMed2006

Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines.

In light of the poor prognosis for ovarian cancer patients, the research continues for innovative and efficacious treatment modalities. Along with surgical and chemotherapeutic regimens, gene therapy has emerged as one of the leading contenders in the treatment armamentarium. Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. However, the biological function of Hepsin expression remains unclear. Apoptotic cell was increasingly common among higher proportions of Hepsin transfectants. We discovered that first-time stable transfectants of Hepsin significantly inhibited cell growth in the monolayer, anchorage-independent cell growth in the soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines. These results demonstrated that Hepsin has a potential therapeutic effect that inhibits through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Our findings in this study identify Hepsin as a target for new approaches in ovarian cancer treatment.

Animals↗
PubMed2005

Risk factors for early and late postoperative complications of patients with endometrial cancer.

OBJECTIVE: We have routinely performed staging with pelvic and/or paraaortic lymphadenectomy in patients with endometrial cancer having moderate to high risk for lymph node metastasis. The aim of this study was to investigate the risk factors for the occurrence of early and late postoperative complications in patients managed primarily by surgery in our institution. STUDY DESIGN: Two-hundred and fifty-nine consecutive cases of endometrial cancer were enrolled in the study. Past history, body mass index, type of surgery, intraoperative findings, and follow-up information were collected from patient charts. Of these, 200, 127, and 30 patients underwent systematic pelvic lymphadenectomy, systematic paraaortic lymphadenectomy, and radical hysterectomy, respectively. The median numbers of dissected pelvic and paraaortic lymph nodes were 32 and 14, respectively. RESULTS: None of the complications resulted in death. Of the study population, 36 early complications and 34 late complications occurred. Overall 65 patients (25.1%) had at least one complication. Multivariate analysis revealed that a longer operative time and paraaortic lymphadenectomy were independent predictors for the occurrence of early and late postoperative complications, respectively. CONCLUSIONS: Since the therapeutic value of lymphadenectomy is still under evaluation, the indications for systematic pelvic and paraaortic lymphadenectomy should be carefully considered.

Adult↗
PubMed2005

The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion.

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of phase I and phase II drug-metabolizing enzymes, as well as members of the drug transporter family, including multiple drug resistance (MDR) 1, which has a major role in multidrug resistance. Previously, we have demonstrated that steroid/xenobiotics metabolism by tumor tissue through the PXR-cytochrome P-450 3A (CYP3A) pathway might play an important role in endometrial cancer. In this study, we examined which endocrine-disrupting chemicals (EDCs) and anticancer agents might be ligands for PXR and whether these chemicals enhanced PXR-mediated transcription through two different PXR-responsive elements (PXREs), CYP3A4 and MDR1, in endometrial cancer cell lines. Some steroids/EDCs strongly activated PXR-mediated transcription through the CYP3A4-responsive element compared with the MDR1-responsive element, whereas these steroids/EDCs also enhanced the CYP3A4 expression compared with the MDR1 expression. In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. We also analyzed how these ligands regulated PXR-mediated transcription through two different PXREs. In the presence of PXR ligands, there was no difference in the DNA binding affinity of the PXR/retinoid X receptor heterodimer to each PXRE, but there were different interactions of the coactivator to each PXR/PXRE complex. These data suggested that PXR ligands enhanced PXR-mediated transcription in a ligand- and promoter-dependent fashion, which in turn differentially regulated the expression of individual PXR targets, especially CYP3A4 and MDR1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia.

BACKGROUND: Numerous recent reports demonstrated that changes in serum levels of angiogenesis-related factors were associated with preeclampsia. Here, we determined the serum concentration of angiopoietin-2 (Ang-2), a natural antagonist of angiopoietin-1 (Ang-1) involved in promoting angiogenesis in the presence of angiogenic stimuli such as vascular endothelial growth factor (VEGF), in women with preeclampsia. METHODS: The levels of serum Ang-2 and Tie-2, a receptor for Ang-1 expressed on endothelial cells, were determined by enzyme-linked immunosorbent assay. RESULTS: The concentrations of serum Ang-2 were significantly elevated in healthy pregnant women (18.9 ng/mL) as compared to nonpregnant women or women in postpartum period. Increase in the levels of serum Ang-2 was significantly suppressed in preeclamptic women (4.5 ng/mL). The serum Ang-2 concentrations inversely correlated with gestational age in healthy pregnant women, but not in preeclamptic women. The serum Ang-2 concentrations positively correlated with placental weight or mean blood pressure (BP) in healthy pregnant women, but not in preeclamptic women. The serum Ang-2 concentrations inversely correlated with proteinuria in preeclamptic women. The serum concentrations of Tie-2 were not significantly different between preeclamptic and nonpreeclamptic women. CONCLUSIONS: These results suggest the potential requirement of circulating Ang-2 in proper formation of placental vasculatures during pregnancy. Although we cannot exclude the possibility that suppression in the increase of serum Ang-2 levels during pregnancy in preeclampsia as a consequence rather than a cause, measurement of serum Ang-2 concentration in pregnant women may serve as a useful marker in the diagnosis and potentially in predicting subsequent development of preeclampsia.

Adult↗
PubMed2005

Nafamostat preserves neutrophil deformability and reduces microaggregate formation during simulated extracorporeal circulation.

BACKGROUND: Initial sequestration of activated neutrophils and platelet microaggregates in capillaries are responsible for the inflammatory response associated with cardiopulmonary bypass. The study assesses the inhibitory effects of nafamostat mesilate on neutrophil and platelet activation, and on the neutrophil deformability change and microaggregate formation during simulated extracorporeal circulation. METHODS: Fresh heparinized human blood was recirculated for 120 minutes in a membrane oxygenator and a roller pump with and without nafamostat (1.0 mg bolus plus 8.0 mg/h infusion; n = 10 for each group). Neutrophil and platelet counts and platelet aggregation were measured. CD11b, L-selectin, and cytoplasmic F-actin of neutrophils were measured by flow cytometry. The microchannel transit time of whole blood was measured as a marker of neutrophil deformability and microaggregate formation. Neutrophil elastase and complement C4d were measured using enzyme immunoassay. RESULTS: Nafamostat preserved platelet counts and inhibited platelet aggregation. Nafamostat significantly reduced neutrophil elastase release at 120 minutes of recirculation, and F-actin expression at 30 and 60 minutes. The drug did not modulate the changes of CD11b, L-selectin, or C4d. Whole blood filterability was significantly preserved by nafamostat at 30 and 120 minutes. CONCLUSIONS: Nafamostat preserves blood filterability during recirculation, possibly by suppression of F-actin expression and platelet activation. Nafamostat may reduce neutrophil sequestration and microaggregate formation in the microcirculation during cardiopulmonary bypass.

Benzamidines↗
PubMed2005

Sivelestat reduces inflammatory mediators and preserves neutrophil deformability during simulated extracorporeal circulation.

BACKGROUND: Neutrophil is a major focus in efforts to ameliorate the systemic inflammatory response associated with cardiopulmonary bypass. Neutrophil elastase is a powerful proteolytic enzyme, and plays a pivotal role in the development of the inflammatory response. This study assesses the inhibitory effects of sivelestat, a highly specific neutrophil elastase inhibitor, on elastase levels, cytokine production, and the functional changes of neutrophils in a simulated extracorporeal circulation model. METHODS: Simulated recirculation was established by recirculating heparinized (3.75 U/mL) human blood for 120 minutes in an oxygenator and a roller pump circuit with and without 100 micromol/L of sivelestat (n = 7 for each group). Neutrophil elastase and interleukin-8 were measured with an enzyme immunoassay. Neutrophil deformability was evaluated by simulated microcapillaries. The neutrophil F-actin and the expression of CD11b and L-selectin were measured by flow cytometry. RESULTS: Sivelestat reduced both neutrophil elastase levels (p = 0.0006) and interleukin-8 production (p < 0.0001) at 120 minutes of recirculation. Sivelestat also significantly preserved neutrophil deformability (p = 0.017) and reduced F-actin expression (p = 0.0037). The drug did not modulate the changes of CD11b or L-selectin. CONCLUSIONS: This study suggests that specific elastase inhibition with sivelestat could be a feasible therapeutic strategy for patients undergoing cardiopulmonary bypass to attenuate neutrophil-derived inflammatory response and organ injuries.

Actins↗
PubMed2005

Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation.

OBJECTIVE: Cardiopulmonary bypass is associated with systemic inflammatory response syndrome and risk of multiorgan injury mediated by activated leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in leukocytes and plays a key role in the regulation of leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on functional changes of monocytes during simulated extracorporeal circulation. METHODS AND RESULTS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with or without 10 micromol/L of rolipram. L-selectin and CD11b expression of monocytes were measured with flow cytometry. C4d fragment, Bb fragment, C5b-9, and interleukin-6 were measured with enzyme immunoassay. Rolipram reduced the increase in CD11b expression and the decrease in L-selectin expression of monocytes in response to simulated extracorporeal circulation. Rolipram inhibited the increase in C4d fragment and interleukin-6, but it did not affect the increase in Bb fragment or C5b-9. CONCLUSION: Rolipram inhibited changes in adhesion molecule expression and interleukin-6 release by activated monocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Loss of cell-surface heparan sulfate expression in both cervical intraepithelial neoplasm and invasive cervical cancer.

OBJECTIVE: Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans (HS-GAG) and most of its biological functions are considered to be associated with this process. The aims of this study are to investigate its expression in cervical neoplasms. METHODS: We investigated the expression of both the syndecan-1 core protein and cell-surface HS-GAG by immunohistochemistry in 53 cervical intraepithelial neoplasm (CIN), 19 microinvasive, 143 invasive cervical cancers, and 29 metastatic lymph node samples, and analyzed correlations with various clinicopathological features. RESULTS: The progression of CIN to early invasive cancer was found to associate with reduced levels of both syndecan-1 and HS-GAG expression. In squamous cell carcinomas, HS-GAG expression was significantly lower in cases with lymph-vascular space invasion. Additionally, the overall survival rates for patients exhibiting low HS-GAG expression was significantly lower than patients exhibiting high HS-GAG expression (P = 0.019). Low HS-GAG expression in positive nodes was determined to be a disease-free and overall survival prognostic factor (P = 0.028 and P = 0.018, respectively). CONCLUSION: The loss of syndecan-1 and HS-GAG expression is an early event in cervical carcinogenesis. The loss of HS-GAG expression particularly in positive nodes can serve as an indicator of aggressive disease potential and poor prognosis in patients with invasive cervical cancer.

Adult↗
PubMed2005

Impaired uterine perfusion associated with metabolic disorders in women with polycystic ovary syndrome.

BACKGROUND: Risk factors for cardiovascular disease, including chronic anovulation, obesity, hyperandrogenism, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS). We evaluated uterine perfusion and its correlation with clinical and biochemical parameters in women with PCOS. METHODS: We performed a pulsed Doppler study on uterine arterial blood flow in 25 women with PCOS and 45 control women with regular menstrual cycles. PCOS was diagnosed based on oligomenorrhea, polycystic ovaries determined by means of ultrasonography, and elevated luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio. RESULTS: Women with PCOS had a significantly higher body mass index (BMI) and serum testosterone, and showed insulin resistance and dyslipidemia, including increased total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C). The uterine arterial pulsatility index (PI) in women with PCOS was significantly higher than that in the control women during the follicular phase. The PI was correlated with BMI, LH/FSH ratio, or LDL-C/HDL-C ratio, whereas it was inversely correlated with the HDL-C level. Women with PCOS had reduced endometrial thickness and elevated uterine arterial PI in the luteal phase, in which implantation occurs. CONCLUSIONS: Elevation of uterine arterial blood flow resistance is associated with risk factors for cardiovascular events. Furthermore, the impaired uterine perfusion in the luteal phase may cause endometrial dysfunction in women with PCOS.

Adult↗
PubMed2005

Intracardiac lead fracture in an implantable cardioverter-defibrillator.

A patient with an implantable cardioverter-defibrillator (ICD) experienced inappropriate shocks. X-rays revealed that the ventricular lead was fractured at a point, which seemed to be in a mechanical stress-free space in the heart. Multiple leads were entwined making a short flexible section sandwiched between the entwined area and the stiff coil susceptible to the stress from heart beats. The present case shows that indirect concentrated stress caused by restriction of lead flexibility can result in lead fracture. Upon implanting multiple endocardial leads, attention should be given to the relative position of each lead.

Adult↗
PubMed2005

Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

It is well known that antecedent term delivery and metastasis to sites other than the lungs and vagina are high risk factors for patients with gestational trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who presented with brain and lung metastases after term delivery and was treated by EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term. Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On admission to our hospital, she had lesions in the uterus, lungs and brain as well as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated as first-line chemotherapy and the patient achieved complete remission after 7 courses. Treatment was terminated after 11 courses and maintained with etoposide (25 mg/day) for 6 months. The patient has remained in complete remission for more than 16 years without other adjuvant therapies. We believe that EMA-CO can currently be considered the regimen of first choice for most high-risk patients with gestational trophoblastic neoplasia in view of its effectiveness and excellent tolerability.

Adult↗